Marius SUDOL
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  Marius SUDOL  
  Lab Location: NUS Campus, Physiology Department - Block MD9. Level 3, SG117597 and Mechanobiology Institute, T-Lab, Level 10, 5A Engineering Drive 1, SG 117411


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  Key Publications  

Sudol, M. (2012)
WW Domains in the Heart of Smad Signaling.
Structure (Cell), 20, 1619-1620

Gaffney, C.J., Oka, T., Mazack, V., Hilman, D., Gat, U., Muramatsu, T., Inazawa, J., Golden, A., Carey, D.J., Farooq, A., Tromp, G., Sudol, M. (2012)
Identification, Basic Characterization and Evolutionary Analysis of Differentially Spliced mRNA Isoforms of Human YAP1 Gene.
Gene 509, 215-222.

Sudol, M. Shields, D., and Farooq, A., (2012)
Structures of YAP Protein Domains Reveal Promising Targets for Development of New Cancer Drugs.
Seminars in Cell & Dev Biol. 23, 827-833.

Oka, T., Schmitt, A.P., and Sudol, M. (2012)
Opposing Roles of Angiomotin Like 1 and Zona Occludens-2 on Pro-apoptotic Function of YAP. 
Oncogene, 31, 128-134.

Sudol, M. (2011)
From Rous Sarcoma Virus to Plasminogen Activator, Src Oncogene and Cancer Management.
Oncogene, 30, 3003-3010.

Oka, T., Remue, E., Meerschaert, K., Vanloo, B., Boucherie, C., Gfeller, D., Bader, G.D., Sidhu, S., Vandekerckhove, J., Gettemans, J., Sudol, M. (2010)
Functional Complex Between YAP2 and ZO-2 is PDZ Domain Dependent, Regulates YAP2 Nuclear Localization and Signaling. Biochemical J, 432, 461-72 (THIS ARTICLE WAS SELECTED BY FACULTY BIOLOGY 1000 in 2011).

Sudol, M., and Harvey, K. (2010) The Modularity in the Hippo Signaling Pathway.
, 35, 627-633.

Tapia, V.E., Nicolaescu, E. McDonald, C.B., Musi, V., Oka, T., Inayoshi, Y., Satteson A.C., Mazack, V., Humbert, J., Gaffney, J.C., Beullens, M., Schwartz, C.E., Landgraf, C., Volkmer, R., Pastore, A., Farooq, A., Bollen, M., and Sudol, M. (2010).
The Y65C Missense Mutation in the WW Domain of the Golabi-Ito-Hall Syndrome Protein PQBP1 Affects Its Binding Activity and Deregulates Pre-mRNA Splicing. J. Biol. Chem. 285, 19391-19401.

Oka, T., Mazack, V., and Sudol, M. (2008)
Mst2 and Lats Kinases Regulate Apoptotic Function of YAP.
J. Biol. Chem. 283, 27534-27546.

Masker, K., Golden, A., Gaffney, C., Mazack, V., Schwindinger, W., Zhang, W., Wang, L-H, Carey, DJ., and Sudol, M. (2007) Transcriptional Profile of Rous Sarcoma Virus Transformed Chicken Embryo Fibroblasts Reveals New Signaling Targets of Viral-src.
Virology, 364, 10-20.

Komuro, A., Nagai, M. Navin, N. and Sudol, M. (2003)
WW Domain-containing Protein YAP Associates with ErbB-4 and Acts as a Co-transcriptional Activator for the Carboxy-terminal Fragment of ErbB4 that Translocates to the Nucleus.
J. Biol Chem. 278, 33334-33341





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  Marius SUDOL

Marius Sudol earned his PhD degree in 1983 at The Rockefeller University in NYC, USA, in molecular and cellular biology and continued on at his Alma Mater as a postdoctoral fellow and faculty member until he became an Associate Professor at Mount Sinai School of Medicine in 1995. In 2004, he moved his laboratory to a private research institute, Weis Center for Research, at Geisinger Health Systems in Pennsylvania, while continuing his academic association with the Mount Sinai School of Medicine in NYC as an adjunct faculty member in the Medicine Department. In 2014, he joined the Department of Physiology at the National University of Singapore with joint appointments at the Mechanobiology Institute and the IMCB. He is actively involved in leading the Protein Modules Consortium and serves on Editorial Boards of several journals including “Oncogene”, “Science Signaling” and “Journal of Biological Chemistry”.


Synopsis of Research


Marius Sudol was trained as a molecular oncologist. Among his most significant achievements to date are the identification of a modular protein domain, known as the WW domain, and the characterization of its cognate ligands. In 2004, together with a research team at AxCell-Cytogen company, Marius Sudol reported the first comprehensive protein interaction map for a human modular domain. Today, the WW domain is known to mediate critical signals in tumor suppressor networks including the Hippo signaling pathway. More importantly, syndromes such as the Golabi-Ito-Hall syndrome of intellectual disability and Liddle syndrome of hypertension are caused by loss-of-function point mutations in the WW domain or its cognate ligands.
Over the course of his scientific career spanning more than three decades, Marius Sudol has authored 140 publications (see Google Scholar), including original research articles and invited reviews in refereed journals as well as numerous book chapters. His current work focuses on the role of WW domain-containing proteins in the Hippo tumor suppressor network and Golabi-Ito-Hall syndrome of intellectual disability.

Figure Legend: LEFT PANEL is a general scheme of the Hippo pathway in Drosophila fly and in human. For details see a review by Harvey and Sudol in TiBS (2010, Volume 35, pages 627-633.).  The main question that we ask experimentally is: How a tight junction protein, ZO2, which is depicted in red, could act as a shuttle that regulates YAP translocation to the nucleus?  Being a bona fide structural protein that is integral to the architecture and function of tight junctions, ZO2 has also emerged as a transcriptional co-factor that affects gene expression. Hippo pathway must sense the status of cell-to-cell junctions via ZO2-YAP shuttle.

RIGHT PANEL is composite cartoon of a point mutation in the WW domain of brain factor, named PQBP1, that regulates mRNA splicing.  The Y to C amino acid substitution mutation is a loss of function mutation for the WW domain, which results in intellectual disability (ID) syndrome named as Golabi-Ito-Hall (GIH) syndrome. The GIH syndrome phenocopies a severe form of autism. For more details see a review by Sudol et al., in FEBS Letters, (2012, Volume 586, pages 2795-2799). By deciphering which mRNAs in the brain of GIH patients are changed, compared to normal brains we should get insight into molecular processes that underlie intellectual disability and autism.

-Hippo-YAP Animal Model

Hippo-YAP tumor suppressor pathway is regulated by multiple WW domain-containing proteins. One such protein is YAP, the major effector of the pathway, whose translocation to the cell nucleus is critical for its activity as a transcriptional co-activator that promotes robust proliferation of cells.  We have shown that YAP’s PDZ binding motif is required for its translocation from the cytoplasm to the nucleus and that one of the shuttle proteins for YAP is a PDZ domain-containing protein, ZO2.  We have  generated YAP knock-in mice without the PDZ binding motif.  Together with Walter Hunziker and Wanjin Hong, we analyze these mutant mice by genetic crosses with ZO2 knock-out heterozygotes to reveal the most likely signaling connection between Hippo-YAP pathway and cell-to-cell junctional complexes.

-Golabi-Ito-Hall Syndrome Animal Mode

A single point mutation in the WW domain of PQBP1 gene, which encodes a brain-enriched mRNA splicing factor, causes mental retardation that phenocopies severe form of autism. Using cells derived from GIH patients, we have documented that the causative mutation in the PQBP1 gene is a ‘loss of function’ mutation that compromises the complex of the WW domain with cognate splicing factors. We are in the process of generating an animal model of the GIH syndrome to investigate global changes in mRNA processing in the affected brains.